A technique is known that inhibits gene expression by targeting an mRNA transcribed from the gene. RNA interference (hereinafter, also referred to as “RNAi”) is a method for specifically inhibiting a gene expression by using a phenomenon in which a short complementary double-stranded RNA fragment (siRNA) promotes degradation of mRNA having the complementary sequence (Non-Patent Document 1). Antisense nucleic acid acts to form a double strand with an mRNA and inhibits the synthesis of a protein encoded by the mRNA. These techniques have made it possible to intentionally and specifically inhibit expression of any gene of a known base sequence, and revealed the usefulness of antisense nucleic acids and siRNAs as nucleic acid drugs. The synthesis methods of antisense nucleic acid and siRNA have been established, and these molecules can be produced in comparatively reasonable price.
Cancer occurs when normal cells transform into cancer cells due to functional abnormalities in molecules (nucleic acids, proteins) produced by genes. Large numbers of molecules are involved in the survival and proliferation of cancer cells, then the survival, proliferation, and tumorigenicity of cancer cells can be inhibited by finding which of these molecules have important roles, and inhibiting the expression of such important molecules. Thus, once molecules of which inhibition prevents the survival, proliferation, and tumorigenicity of cancer cells are identified, it would be possible to develop a molecular therapy targeting these molecules. further, using a specific short double-stranded RNA for the inhibition of molecule expression enables a siRNA of a specific sequence to be used as a nucleic acid drug.
It is known that pancreatic cancer is refractory worldwide. In Japan, pancreatic cancer ranks fifth as the cause of death among different organ cancers analyzed by statistics. As of year 2000, pancreatic cancer has affected 20,045 individuals, and killed 19,093. The disease is so malignant that most of the affected individuals die. The number of affected individuals is on the rise every year, tripling in the 25-year period from 1975 to 2000 (cancer statistics, Foundation for Promotion of Cancer Research).
Globally, pancreatic cancer is the fifth leading cause of death in the Western countries, and has the highest mortality among malignant tumors, with the five-year survival rate of only 4% (for example, Non-Patent Document 2). These facts indicate that it is difficult with the current medical technology to provide a cure for pancreatic cancer, and that development of an effective novel therapy is required.
Inventions are known that concern medicaments intended to treat pancreatic cancer under the mechanism by which expression of specific genes are inhibited (Patent Documents 1 and 2). However, Patent Document 1 is intended to inhibit expression of apoptosis-inhibiting genes (Bcl-2 family), and the target is not limited to pancreatic cancer. Further, only an RNA molecule needs to be accurately introduced into cancer cells in order to cause apoptosis specifically in cancer cells (i.e., not to cause normal-cell death). Patent Document 2, on the other hand, concerns CST6 gene and GABRP gene associated with pancreatic cancer. While increased expression of these genes in pancreatic cancer patients has been confirmed, it remains unconfirmed whether the increased gene expression represents a cause of pancreatic cancer. That is, while it is possible to diagnose pancreatic cancer or predict the risk of pancreatic cancer by the measurement of gene expression, it remains totally uncertain whether inhibition of gene expression has any possibility of treating pancreatic cancer.
The following information is known for SON, MCM5, WDR5, PBK and CENPA genes. SON (SON DNA binding protein) is reported as a DNA binding molecule, but detailed functions remain elusive (Non-Patent Documents 3 to 5). MCM5 (minichromosome maintenance complex component 5) is a molecule that functions as a DNA replication factor (Non-Patent Document 6). WDR5 (WD repeat domain 5) associates with histone 1-13 lysine 4, and is essential for development (Non-Patent Document 7). PBK (PDZ binding kinase) is a phosphorylating enzyme that belongs to MAP2K group, and involved in DNA damaging reaction (Non-Patent Document 8). CENPA (centromere protein A) corresponds to histone H3 that forms a chromosome centromere, and is essential for the kinetochore (Non-Patent Document 9). However, involvement of these genes in the survival, proliferation and tumorigenicity of pancreatic cancer cells is not known.
Previously, the inventor of the present application has identified a signal transduction-related gene group in pancreatic cancer cells (Non-Patent Document 10). However, a relationship between these genes and the proliferation, survival and tumorigenicity of pancreatic cancer cells is completely unknown.    Patent Document 1: JP2004-519457    Patent Document 2: JP2009-505632    Non-Patent Document 1: Fire et al. Nature 391: 806-11, 1998    Non-Patent Document 2: Zervos EE, et al. Cancer Control 11: 23-31, 2004    Non-Patent Document 3: Mattioni et al. Chromosome 101: 618-624, 1992    Non-Patent Document 4: Wynn at al. Genomics 68: 57-62, 2000    Non-Patent Document 5: Ahn at al. PNAS 105: 17103-8, 2008)    Non-Patent Document 6: Snyder at al. PNAS 102: 14539-44, 2005    Non-Patent Document 7: Wysocka at al. Cell 121: 859-72, 2005    Non-Patent Document 8: Nandi et al. Biochem Biophys Res Commun 358: 181-188, 2007    Non-Patent Document 9: McClelland at al. EMBO J 26:5033-5047, 2007    Non-Patent Document 10: Furukawa et al. Oncogene 25: 4831-9, 2006